Body temperature is highly regulated in mammals. However, thermal biology in smaller mammals (such as mice) is different from that in larger mammals (such as adult humans). For example, when mice are singly housed at room temperature, about half of caloric intake is burned to maintain body temperature (facultative thermogenesis), while humans require little facultative thermogenesis. Upon fasting, mice can reduce their body temperature by >10 C, while humans with extreme starvation lower body temperature by only 0.2 C. We are exploring the use of body temperature as an indicator of the perceived metabolic status of the mouse. For example, what is the effect on body temperature of a genetic manipulation or drug treatment? What genetic manipulations or drug treatments cause dissociation of body temperature from nutritional status? What are the neurotransmitters and neural mechanisms involved? Progress in FY2015 includes the following: We published a study that quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. Environmental temperature was varied from 4 C to 33 C, with continuous monitoring of body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3 null, lipodystrophic). Body temperature depended most on circadian phase and physical activity, but also on environmental temperature. The amounts of energy expenditure due to basal metabolic rate (calculated via a novel method), thermic effect of food, physical activity, and cold-induced thermogenesis were determined as a function of environmental temperature. The measured resting defended body temperature matched that calculated from the energy expenditure using Fouriers law of heat conduction. Mice defended a higher body temperature during physical activity. The cost of the warmer body temperature during the active phase is 4 to 16% of total daily energy expenditure. Parameters measured in diet-induced obese and Brs3 null mice were similar to controls. The high post-mortem heat conductance demonstrates that most insulation in mice is via physiological mechanisms. At 22 C, cold-induced thermogenesis is 120% of basal metabolic rate. The higher body temperature during physical activity is due to a higher set point, not simply increased heat generation during exercise. Most insulation in mice is via physiological mechanisms, with little from fur or fat. Our analysis suggests that the definition of the upper limit of the thermoneutral zone should be re-considered. Measuring body temperature informs interpretation of energy expenditure data and improves the predictiveness and utility of the mouse to model human energy homeostasis.